IDH mutation in glioma: molecular mechanisms and potential therapeutic targets

IDH1-R132H acts as a tumor suppressor in glioma via epigenetic up-regulation of the DNA damage response

(2019) Felipe J. Núñez et al.   Science Translational Medicine

Combination of PARP inhibitor and temozolomide to suppress chordoma progression

(2019) Xiaoyu Cao et al.   JOURNAL OF MOLECULAR MEDICINE-JMM

Methylation and transcription patterns are distinct in IDH mutant gliomas compared to other IDH mutant cancers

(2019) Dusten Unruh et al.   Scientific Reports

Brusatol, an NRF2 inhibitor for future cancer therapeutic

(2019) Sabrina J. Cai et al.   Cell and Bioscience

Mutant IDH Sensitizes Gliomas to Endoplasmic Reticulum Stress and Triggers Apoptosis via miR-183-Mediated Inhibition of Semaphorin 3E

(2019) Ying Zhang et al.   CANCER RESEARCH

Blockade of glutathione metabolism in IDH1-mutated glioma

(2019) Xiaoying Tang et al.   MOLECULAR CANCER THERAPEUTICS

Metabolic Reprogramming Associated with Aggressiveness Occurs in the G-CIMP-High Molecular Subtypes of IDH1mut Lower Grade Gliomas

(2019) Ruiz-Rodado Victor et al.   NEURO-ONCOLOGY

Autocrine BMP4 Signaling Enhances Tumor Aggressiveness via Promoting Wnt/β-Catenin Signaling in IDH1-mutant Gliomas

(2019) Yiqiang Zhou et al.   Translational Oncology

2-Hydroxyglutarate-Mediated Autophagy of the Endoplasmic Reticulum Leads to an Unusual Downregulation of Phospholipid Biosynthesis in Mutant IDH1 Gliomas

(2018) Pavithra Viswanath et al.   CANCER RESEARCH

Targeting NAD+/PARP DNA Repair Pathway as a Novel Therapeutic Approach toSDHB-Mutated Cluster I Pheochromocytoma and Paraganglioma

(2018) Ying Pang et al.   CLINICAL CANCER RESEARCH

IDH1 Arg-132 mutant promotes tumor formation through down-regulating p53

(2018) Bin Jiang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair

(2018) Parker L. Sulkowski et al.   NATURE GENETICS

Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate

(2018) Lukas Bunse et al.   NATURE MEDICINE

Temozolomide-associated hypermutation in gliomas

(2018) Serah Choi et al.   NEURO-ONCOLOGY

Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML

(2018) Courtney D. DiNardo et al.   NEW ENGLAND JOURNAL OF MEDICINE

Double-barreled gun: Combination of PARP inhibitor with conventional chemotherapy

(2018) Yanxin Lu et al.   PHARMACOLOGY & THERAPEUTICS

Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers

(2018) Janeta Popovici-Muller et al.   ACS Medicinal Chemistry Letters

Pharmacodynamics of mutant-IDH1 inhibitors in glioma patients probed by in vivo 3D MRS imaging of 2-hydroxyglutarate

(2018) Ovidiu C. Andronesi et al.   Nature Communications

Oncogenic IDH1 Mutations Promote Enhanced Proline Synthesis through PYCR1 to Support the Maintenance of Mitochondrial Redox Homeostasis

(2018) Kate E.R. Hollinshead et al.   Cell Reports

Mutant IDH1 Promotes Glioma Formation In Vivo

(2018) Beatrice Philip et al.   Cell Reports

The IDH1 Mutation-Induced Oncometabolite, 2-Hydroxyglutarate, May Affect DNA Methylation and Expression of PD-L1 in Gliomas

(2018) Luyan Mu et al.   Frontiers in Molecular Neuroscience

PD-1 ( PDCD1 ) Promoter Methylation Is a Prognostic Factor in Patients With Diffuse Lower-Grade Gliomas Harboring Isocitrate Dehydrogenase ( IDH ) Mutations

(2018) Lea Kristin Röver et al.   EBioMedicine

Beyond Brooding on Oncometabolic Havoc in IDH-Mutant Gliomas and AML: Current and Future Therapeutic Strategies

(2018) Hanumantha Madala et al.   Cancers

Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma

(2018) Samuel K. McBrayer et al.   CELL

A mutation-specific peptide vaccine targeting IDH1R132H in patients with newly diagnosed malignant astrocytomas: A first-in-man multicenter phase I clinical trial of the German Neurooncology Working Group (NOA-16).

(2018) Michael Platten et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase 1 study of AG-881, an inhibitor of mutant IDH1/IDH2, in patients with advanced IDH-mutant solid tumors, including glioma.

(2018) Ingo K. Mellinghoff et al.   JOURNAL OF CLINICAL ONCOLOGY

Demethylation and epigenetic modification with 5-azacytidine reduces IDH1 mutant glioma growth in combination with temozolomide

(2018) Alex Shimura Yamashita et al.   NEURO-ONCOLOGY

The R132H mutation in IDH1 promotes the recruitment of NK cells through CX3CL1/CX3CR1 chemotaxis and is correlated with a better prognosis in gliomas

(2018) Feifei Ren et al.   IMMUNOLOGY AND CELL BIOLOGY

Oncogenic R132 IDH1 Mutations Limit NADPH for De Novo Lipogenesis through (D)2-Hydroxyglutarate Production in Fibrosarcoma Cells

(2018) Mehmet G. Badur et al.   Cell Reports

Targeting IDH1-Mutated Malignancies with NRF2 Blockade

(2018) Yang Liu et al.   JNCI-Journal of the National Cancer Institute

Mutant IDH1 regulates the tumor-associated immune system in gliomas

(2017) Nduka M. Amankulor et al.   GENES & DEVELOPMENT

Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas

(2017) Gary Kohanbash et al.   JOURNAL OF CLINICAL INVESTIGATION

Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo

(2017) A Chaturvedi et al.   LEUKEMIA

Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence

(2017) Sevin Turcan et al.   NATURE GENETICS

Clonal expansion and epigenetic reprogramming following deletion or amplification of mutantIDH1

(2017) Tali Mazor et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of Bcl-xL

(2017) Georg Karpel-Massler et al.   Nature Communications

PLK1 inhibition enhances temozolomide efficacy in IDH1 mutant gliomas

(2017) Robert F. Koncar et al.   Oncotarget

In silico gene expression analysis reveals glycolysis and acetate anaplerosis in IDH1 wild-type glioma and lactate and glutamate anaplerosis in IDH1-mutated glioma

(2017) Mohammed Khurshed et al.   Oncotarget

A Brain Penetrant Mutant IDH1 Inhibitor Provides In Vivo Survival Benefit

(2017) Johnny Kopinja et al.   Scientific Reports

Glutamate and α-ketoglutarate: key players in glioma metabolism

(2016) Andreas Maus et al.   AMINO ACIDS

Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma

(2016) Michele Ceccarelli et al.   CELL

Rapid Conversion of Mutant IDH1 from Driver to Passenger in a Model of Human Gliomagenesis

(2016) T.-C. A. Johannessen et al.   MOLECULAR CANCER RESEARCH

Inhibiting glutaminase in acute myeloid leukemia: metabolic dependency of selected AML subtypes

(2016) Polina Matre et al.   Oncotarget

Hyperpolarized 13 C MR imaging detects no lactate production in mutant IDH1 gliomas: Implications for diagnosis and response monitoring

(2016) Myriam M. Chaumeil et al.   NeuroImage-Clinical

Molecular and clinical characterization of PD-L1 expression at transcriptional level via 976 samples of brain glioma

(2016) Zheng Wang et al.   OncoImmunology

Extreme Vulnerability of IDH1 Mutant Cancers to NAD+ Depletion

(2015) Kensuke Tateishi et al.   CANCER CELL

Radioprotection of IDH1-Mutated Cancer Cells by the IDH1-Mutant Inhibitor AGI-5198

(2015) R. J. Molenaar et al.   CANCER RESEARCH

Idh1 protects murine hepatocytes from endotoxin-induced oxidative stress by regulating the intracellular NADP+/NADPH ratio

(2015) M Itsumi et al.   CELL DEATH AND DIFFERENTIATION

Anti–PD-1/PD-L1 therapy of human cancer: past, present, and future

(2015) Lieping Chen et al.   JOURNAL OF CLINICAL INVESTIGATION

Insulator dysfunction and oncogene activation in IDH mutant gliomas

(2015) William A. Flavahan et al.   NATURE

Physiological and pathophysiological roles of NAMPT and NAD metabolism

(2015) Antje Garten et al.   Nature Reviews Endocrinology

Inhibition of mutant IDH1 decreases D-2-HG levels without affecting tumorigenic properties of chondrosarcoma cell lines

(2015) Johnny Suijker et al.   Oncotarget

Oncometabolite D-2-Hydroxyglutarate Inhibits ALKBH DNA Repair Enzymes and Sensitizes IDH Mutant Cells to Alkylating Agents

(2015) Pu Wang et al.   Cell Reports

Effective immuno-targeting of the IDH1 mutation R132H in a murine model of intracranial glioma

(2015) Serena Pellegatta et al.   Acta Neuropathologica Communications

5-azacytidine reduces methylation, promotes differentiation and induces tumor regression in a patient-derived IDH1 mutant glioma xenograft

(2015) Alexandra Borodovsky et al.   Oncotarget

Efficient induction of differentiation and growth inhibition in IDH1 mutant glioma cells by the DNMT Inhibitor Decitabine.

(2015) Sevin Turcan et al.   Oncotarget

Mutant IDH1-Driven Cellular Transformation Increases RAD51-Mediated Homologous Recombination and Temozolomide Resistance

(2014) Shigeo Ohba et al.   CANCER RESEARCH

IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism

(2014) A. R. Grassian et al.   CANCER RESEARCH

Targetable Signaling Pathway Mutations Are Associated with Malignant Phenotype in IDH-Mutant Gliomas

(2014) H. Wakimoto et al.   CLINICAL CANCER RESEARCH

Cancer-associated Isocitrate Dehydrogenase 1 (IDH1) R132H Mutation and d-2-Hydroxyglutarate Stimulate Glutamine Metabolism under Hypoxia

(2014) Zachary J. Reitman et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

A vaccine targeting mutant IDH1 induces antitumour immunity

(2014) Theresa Schumacher et al.   NATURE

Quantitative metabolome analysis profiles activation of glutaminolysis in glioma with IDH1 mutation

(2014) Fumiharu Ohka et al.   TUMOR BIOLOGY

Decreasing GSH and increasing ROS in chemosensitivity gliomas with IDH1 mutation

(2014) Jinlong Shi et al.   TUMOR BIOLOGY

A High-Throughput Fluorimetric Assay for 2-Hydroxyglutarate Identifies Zaprinast as a Glutaminase Inhibitor

(2014) A. Elhammali et al.   Cancer Discovery

Autophagy and oxidative stress in gliomas with IDH1 mutations

(2013) Misty R. Gilbert et al.   ACTA NEUROPATHOLOGICA

Isocitrate dehydrogenase 1 mutant R132H sensitizes glioma cells to BCNU-induced oxidative stress and cell death

(2013) Isabelle Vanessa Mohrenz et al.   APOPTOSIS

Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML

(2013) A. Chaturvedi et al.   BLOOD

The Somatic Genomic Landscape of Glioblastoma

(2013) Cameron W. Brennan et al.   CELL

Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations

(2013) Ashkan Emadi et al.   EXPERIMENTAL HEMATOLOGY

What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer

(2013) J.-A. Losman et al.   GENES & DEVELOPMENT

Targeting lactate metabolism for cancer therapeutics

(2013) Joanne R. Doherty et al.   JOURNAL OF CLINICAL INVESTIGATION

TET enzymes, TDG and the dynamics of DNA demethylation

(2013) Rahul M. Kohli et al.   NATURE

The role of iron and reactive oxygen species in cell death

(2013) Scott J Dixon et al.   Nature Chemical Biology

Spontaneous loss of heterozygosity leading to homozygous R132H in a patient-derived IDH1 mutant cell line

(2013) H. A. Luchman et al.   NEURO-ONCOLOGY

Lactate dehydrogenase A silencing in IDH mutant gliomas

(2013) Charles Chesnelong et al.   NEURO-ONCOLOGY

An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells

(2013) D. Rohle et al.   SCIENCE

A heterozygous IDH1R132H/WT mutation induces genome-wide alterations in DNA methylation

(2012) C. G. Duncan et al.   GENOME RESEARCH

IDH mutation impairs histone demethylation and results in a block to cell differentiation

(2012) Chao Lu et al.   NATURE

Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation

(2012) Peppi Koivunen et al.   NATURE

IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype

(2012) Sevin Turcan et al.   NATURE

Glioma cells showing IDH1 mutation cannot be propagated in standard cell culture conditions

(2011) S Piaskowski et al.   BRITISH JOURNAL OF CANCER

Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of α-Ketoglutarate-Dependent Dioxygenases

(2011) Wei Xu et al.   CANCER CELL

Altered cancer cell metabolism in gliomas with mutant IDH1 or IDH2

(2011) Alexandra Borodovsky et al.   CURRENT OPINION IN ONCOLOGY

The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases

(2011) Rasheduzzaman Chowdhury et al.   EMBO REPORTS

IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours

(2011) M Fernanda Amary et al.   JOURNAL OF PATHOLOGY

Metabolism unhinged: IDH mutations in cancer

(2011) John R Prensner et al.   NATURE MEDICINE

An in vivo patient-derived model of endogenous IDH1-mutant glioma

(2011) H. A. Luchman et al.   NEURO-ONCOLOGY

Identification of additional IDH mutations associated with oncometabolite R(−)-2-hydroxyglutarate production

(2011) P S Ward et al.   ONCOGENE

Frequent Mutation of Isocitrate Dehydrogenase (IDH)1 and IDH2 in Cholangiocarcinoma Identified Through Broad-Based Tumor Genotyping

(2011) D. R. Borger et al.   ONCOLOGIST

Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome

(2011) Z. J. Reitman et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas

(2010) Christian Hartmann et al.   ACTA NEUROPATHOLOGICA

The Common Feature of Leukemia-Associated IDH1 and IDH2 Mutations Is a Neomorphic Enzyme Activity Converting α-Ketoglutarate to 2-Hydroxyglutarate

(2010) Patrick S. Ward et al.   CANCER CELL

Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma

(2010) Houtan Noushmehr et al.   CANCER CELL

Leukemic IDH1 and IDH2 Mutations Result in a Hypermethylation Phenotype, Disrupt TET2 Function, and Impair Hematopoietic Differentiation

(2010) Maria E. Figueroa et al.   CANCER CELL

PTEN Loss Compromises Homologous Recombination Repair in Astrocytes: Implications for Glioblastoma Therapy with Temozolomide or Poly(ADP-Ribose) Polymerase Inhibitors

(2010) B. McEllin et al.   CANCER RESEARCH

Inhibition of Glutaminase Preferentially Slows Growth of Glioma Cells with Mutant IDH1

(2010) M. J. Seltzer et al.   CANCER RESEARCH

Molecular mechanisms of “off-on switch” of activities of human IDH1 by tumor-associated mutation R132H

(2010) Bei Yang et al.   CELL RESEARCH

IDH1 and IDH2 Mutations Are Frequent Genetic Alterations in Acute Myeloid Leukemia and Confer Adverse Prognosis in Cytogenetically Normal Acute Myeloid Leukemia With NPM1 Mutation Without FLT3 Internal Tandem Duplication

(2010) Peter Paschka et al.   JOURNAL OF CLINICAL ONCOLOGY

DNA Methylation, Isocitrate Dehydrogenase Mutation, and Survival in Glioma

(2010) Brock C. Christensen et al.   JNCI-Journal of the National Cancer Institute

IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas

(2010) C. Houillier et al.   NEUROLOGY

Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression

(2010) A. Le et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

IDH1 Mutations as Molecular Signature and Predictive Factor of Secondary Glioblastomas

(2009) S. Nobusawa et al.   CLINICAL CANCER RESEARCH

Cancer-associated IDH1 mutations produce 2-hydroxyglutarate

(2009) Lenny Dang et al.   NATURE

IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide

(2009) H. J. Dubbink et al.   NEUROLOGY

IDH1andIDH2Mutations in Gliomas

(2009) Hai Yan et al.   NEW ENGLAND JOURNAL OF MEDICINE

Glioma-Derived Mutations in IDH1 Dominantly Inhibit IDH1 Catalytic Activity and Induce HIF-1 

(2009) S. Zhao et al.   SCIENCE